Evidence for extensive pleiotropy among pharmacogenes.

Oetjens MT, Bush WS, Denny JC, Birdwell K, Kodaman N, Verma A, Dilks HH, Pendergrass SA, Ritchie MD, Crawford DC
Pharmacogenomics. 2016 17 (8): 853-66

PMID: 27249515 · PMCID: PMC5352965 · DOI:10.2217/pgs-2015-0007

AIM - We sought to identify potential pleiotropy involving pharmacogenes.

METHODS - We tested 184 functional variants in 34 pharmacogenes for associations using a custom grouping of International Classification and Disease, Ninth Revision billing codes extracted from deidentified electronic health records of 6892 patients.

RESULTS - We replicated several associations including ABCG2 (rs2231142) and gout (p = 1.73 × 10(-7); odds ratio [OR]: 1.73; 95% CI: 1.40-2.12); and SLCO1B1 (rs4149056) and jaundice (p = 2.50 × 10(-4); OR: 1.67; 95% CI: 1.27-2.20).

CONCLUSION - In this systematic screen for phenotypic associations with functional variants, several novel genotype-phenotype combinations also achieved phenome-wide significance, including SLC15A2 rs1143672 and renal osteodystrophy (p = 2.67 × 10(-) (6); OR: 0.61; 95% CI: 0.49-0.75).

MeSH Terms (13)

Adult African Americans Cytochrome P-450 CYP2C19 Female Genetic Pleiotropy Genome-Wide Association Study Genotype Humans Male Middle Aged Pharmacogenetics Phenotype Symporters

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